PURPOSE: To introduce the heterogeneous multiscale (HetMS) model for Monte Carlo simulations of gold nanoparticle dose-enhanced radiation therapy (GNPT), a model characterized by its varying levels of detail on different length scales within a single phantom; to apply the HetMS model in two different scenarios relevant for GNPT and to compare computed results with others published.METHODS: The HetMS model is implemented using an extended version of the EGSnrc user-code egs_chamber; the extended code is tested and verified via comparisons with recently published data from independent GNP simulations. Two distinct scenarios for the HetMS model are then considered: (a) monoenergetic photon beams (20 keV to 1 MeV) incident on a cylinder (1 cm radius, 3 cm length); (b) isotropic point source (brachytherapy source spectra) at the center of a 2.5 cm radius sphere with gold nanoparticles (GNPs) diffusing outwards from the center. Dose enhancement factors (DEFs) are compared for different source energies, depths in phantom, gold concentrations, GNP sizes, and modeling assumptions, as well as with independently published values. Simulation efficiencies are investigated.RESULTS: The HetMS MC simulations account for the competing effects of photon fluence perturbation (due to gold in the scatter media) coupled with enhanced local energy deposition (due to modeling discrete GNPs within subvolumes). DEFs are most sensitive to these effects for the lower source energies, varying with distance from the source; DEFs below unity (i.e., dose decreases, not enhancements) can occur at energies relevant for brachytherapy. For example, in the cylinder scenario, the 20 keV photon source has a DEF of 3.1 near the phantom's surface, decreasing to less than unity by 0.7 cm depth (for 20 mg/g). Compared to discrete modeling of GNPs throughout the gold-containing (treatment) volume, efficiencies are enhanced by up to a factor of 122 with the HetMS approach. For the spherical phantom, DEFs vary with time for diffusion, radionuclide, and radius; DEFs differ considerably from those computed using a widely applied analytic approach.CONCLUSIONS: By combining geometric models of varying complexity on different length scales within a single simulation, the HetMS model can effectively account for both macroscopic and microscopic effects which must both be considered for accurate computation of energy deposition and DEFs for GNPT. Efficiency gains with the HetMS approach enable diverse calculations which would otherwise be prohibitively long. The HetMS model may be extended to diverse scenarios relevant for GNPT, providing further avenues for research and development.

Additional Metadata
Keywords brachytherapy, dose enhancement, gold nanoparticles, Monte Carlo, multiscale model, radiation therapy
Persistent URL dx.doi.org/10.1002/mp.12061
Journal Medical physics
Citation
Martinov, M.P. (Martin P.), & Thomson, R. (2017). Heterogeneous multiscale Monte Carlo simulations for gold nanoparticle radiosensitization. Medical physics, 44(2), 644–653. doi:10.1002/mp.12061